Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation

Patricia M. Vuguin, Mamdouh H. Kedees, Lingguang Cui, Yelena Guz, Richard W. Gelling, Morris Nejathaim, Maureen J. Charron, Gladys Teitelman

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Abstract

Although glucagon (GLU) plays a pivotal role in glucose homeostasis, its role in the regulation of fetal growth and maturation is poorly understood. These issues were examined in a line of mice with a global deletion of the GLU receptor (Gcgr-/-), which are characterized by lower blood glucose levels and by α- and δ-cell hyperplasia in adults. Ablation of Gcgr was deleterious to fetal survival; it delayed β-cell differentiation and perturbed the proportion of β- to α-cells in embryonic islets. In adults, the mutation inhibited the progression of α-cells to maturity, affected the expression of several β-cell-specific genes, and resulted in an augmentation of the α-, β-, and δ-cell mass. This increase was due to an augmentation in both islet number and in the rate of proliferation of cells expressing GLU or insulin. These findings suggest that GLU participates in a feedback loop that regulates the proportion of the different endocrine cell types in islets, the number of islets per pancreas, and development of the mature α-cell phenotype.

Original languageEnglish (US)
Pages (from-to)3995-4006
Number of pages12
JournalEndocrinology
Volume147
Issue number9
DOIs
StatePublished - 2006

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Glucagon Receptors
Glucagon
Genes
Endocrine Cells
Fetal Development
Hyperplasia
Blood Glucose
Cell Differentiation
Pancreas
Homeostasis
Cell Proliferation
Insulin
Phenotype
Glucose
Mutation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Vuguin, P. M., Kedees, M. H., Cui, L., Guz, Y., Gelling, R. W., Nejathaim, M., ... Teitelman, G. (2006). Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation. Endocrinology, 147(9), 3995-4006. https://doi.org/10.1210/en.2005-1410

Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation. / Vuguin, Patricia M.; Kedees, Mamdouh H.; Cui, Lingguang; Guz, Yelena; Gelling, Richard W.; Nejathaim, Morris; Charron, Maureen J.; Teitelman, Gladys.

In: Endocrinology, Vol. 147, No. 9, 2006, p. 3995-4006.

Research output: Contribution to journalArticle

Vuguin, PM, Kedees, MH, Cui, L, Guz, Y, Gelling, RW, Nejathaim, M, Charron, MJ & Teitelman, G 2006, 'Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation', Endocrinology, vol. 147, no. 9, pp. 3995-4006. https://doi.org/10.1210/en.2005-1410
Vuguin, Patricia M. ; Kedees, Mamdouh H. ; Cui, Lingguang ; Guz, Yelena ; Gelling, Richard W. ; Nejathaim, Morris ; Charron, Maureen J. ; Teitelman, Gladys. / Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation. In: Endocrinology. 2006 ; Vol. 147, No. 9. pp. 3995-4006.
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